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DIFFERENTIAL CYTOTOXIC SENSITIVITY IN MOUSE AND HUMAN CELL LINES EXPOSED TO ORGANOPHOSPHATE INSECTICIDES
Citation:
Veronesi, B. AND M. Ehrich. DIFFERENTIAL CYTOTOXIC SENSITIVITY IN MOUSE AND HUMAN CELL LINES EXPOSED TO ORGANOPHOSPHATE INSECTICIDES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/039 (NTIS PB94137155), 1993.
Description:
Cell lines were used to examine the differential interspecies response (i.e., species selectivity) to organophosphates (OPs). aseline activities of the major target esterase i.e., cholinesterase (ChE), carboxylesterase (CbxE), neurotoxic esterase (NTE) were assayed in mouse and various human neural cell lines and found to be consistently.higher in human derived cells. ytotoxicity data, (neutral red fluorometric assay), collected on both human (SY5Y) and mouse (NB41A3) neuroblastoma clones, indicated that mouse cell lines were consistently more sensitive than human cell lines to equimolar doses of various OP compounds (e.g., mipafox, parathion, paraoxon, DFP, fenthion, fenitrothion). his differential cytotoxic sensitivity was most pronounced in response to compounds requiring metabolic bioactivation (i.e., protoxicants). dditional experiments demonstrated that the NB4lA3 mouse neuroblastoma cell line was more metabolically competent than the Sy5Y human cell line in converting protoxicants (i.e., parathion) to its neurotoxic metabolite (i.e., paraoxon). eta-lymphoblastoids, genetically engineered with human P450 cDNAs, demonstrated higher cytotoxic sensitivity to parathion than unengineered cells, indicating that P450 mono-oxidase activity could influence parathion's bioactivation to its more neurotoxic oxon in culture. hese data suggest that several factors may influence species selectivity in response to OP-related cytotoxicity: intercellular differences in esterase levels, intercellular metabolic differences, and P450 mono-oxidase activity.